Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia

<i>Background</i>: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell ac...

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Main Authors: Isabel Valhondo, Fakhri Hassouneh, Nelson Lopez-Sejas, Alejandra Pera, Beatriz Sanchez-Correa, Beatriz Guerrero, Juan M. Bergua, Maria Jose Arcos, Helena Bañas, Ignacio Casas-Avilés, Joaquin Sanchez-Garcia, Josefina Serrano, Carmen Martin, Esther Duran, Corona Alonso, Rafael Solana, Raquel Tarazona
Format: Article
Language:English
Published: MDPI AG 2020-08-01
Series:Cancers
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Online Access:https://www.mdpi.com/2072-6694/12/8/2171
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author Isabel Valhondo
Fakhri Hassouneh
Nelson Lopez-Sejas
Alejandra Pera
Beatriz Sanchez-Correa
Beatriz Guerrero
Juan M. Bergua
Maria Jose Arcos
Helena Bañas
Ignacio Casas-Avilés
Joaquin Sanchez-Garcia
Josefina Serrano
Carmen Martin
Esther Duran
Corona Alonso
Rafael Solana
Raquel Tarazona
author_facet Isabel Valhondo
Fakhri Hassouneh
Nelson Lopez-Sejas
Alejandra Pera
Beatriz Sanchez-Correa
Beatriz Guerrero
Juan M. Bergua
Maria Jose Arcos
Helena Bañas
Ignacio Casas-Avilés
Joaquin Sanchez-Garcia
Josefina Serrano
Carmen Martin
Esther Duran
Corona Alonso
Rafael Solana
Raquel Tarazona
author_sort Isabel Valhondo
collection DOAJ
description <i>Background</i>: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. <i>Methods</i>: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. <i>Results</i>: NK cells, CD56− T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56− T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1−TIGIT+TACTILE+ NK cells and DNAM-1− TIGIT+TACTILE+ CD56− T cells were associated with a better survival of AML patients. <i>Conclusions</i>: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.
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spelling doaj.art-89084bed6a0d40358fa764ee0452805c2023-11-20T09:06:21ZengMDPI AGCancers2072-66942020-08-01128217110.3390/cancers12082171Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid LeukemiaIsabel Valhondo0Fakhri Hassouneh1Nelson Lopez-Sejas2Alejandra Pera3Beatriz Sanchez-Correa4Beatriz Guerrero5Juan M. Bergua6Maria Jose Arcos7Helena Bañas8Ignacio Casas-Avilés9Joaquin Sanchez-Garcia10Josefina Serrano11Carmen Martin12Esther Duran13Corona Alonso14Rafael Solana15Raquel Tarazona16Immunology Unit, University of Extremadura, 10003 Cáceres, SpainImmunology Unit, University of Extremadura, 10003 Cáceres, SpainImmunology Unit, University of Extremadura, 10003 Cáceres, SpainDepartment of Immunolgy and Allergy, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Cordoba, SpainImmunology Unit, University of Extremadura, 10003 Cáceres, SpainImmunology Unit, University of Extremadura, 10003 Cáceres, SpainDepartment of Hematology, Hospital San Pedro de Alcantara, 10003 Caceres, SpainDepartment of Hematology, Hospital San Pedro de Alcantara, 10003 Caceres, SpainDepartment of Hematology, Hospital San Pedro de Alcantara, 10003 Caceres, SpainDepartment of Hematology, Hospital San Pedro de Alcantara, 10003 Caceres, SpainDepartment of Hematology, Reina Sofia University Hospital, 14004 Córdoba, SpainDepartment of Hematology, Reina Sofia University Hospital, 14004 Córdoba, SpainDepartment of Hematology, Reina Sofia University Hospital, 14004 Córdoba, SpainHistology and Pathology Unit, Faculty of Veterinary, University of Extremadura, 10003 Cáceres, SpainDepartment of Immunolgy and Allergy, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Cordoba, SpainDepartment of Immunolgy and Allergy, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), 14004 Cordoba, SpainImmunology Unit, University of Extremadura, 10003 Cáceres, Spain<i>Background</i>: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. <i>Methods</i>: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. <i>Results</i>: NK cells, CD56− T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56− T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1−TIGIT+TACTILE+ NK cells and DNAM-1− TIGIT+TACTILE+ CD56− T cells were associated with a better survival of AML patients. <i>Conclusions</i>: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.https://www.mdpi.com/2072-6694/12/8/2171acute myeloid leukemiaDNAM-1NK cellsNKT-like cellsTACTILET cells
spellingShingle Isabel Valhondo
Fakhri Hassouneh
Nelson Lopez-Sejas
Alejandra Pera
Beatriz Sanchez-Correa
Beatriz Guerrero
Juan M. Bergua
Maria Jose Arcos
Helena Bañas
Ignacio Casas-Avilés
Joaquin Sanchez-Garcia
Josefina Serrano
Carmen Martin
Esther Duran
Corona Alonso
Rafael Solana
Raquel Tarazona
Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
Cancers
acute myeloid leukemia
DNAM-1
NK cells
NKT-like cells
TACTILE
T cells
title Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_full Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_fullStr Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_full_unstemmed Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_short Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_sort characterization of the dnam 1 tigit and tactile axis on circulating nk nkt like and t cell subsets in patients with acute myeloid leukemia
topic acute myeloid leukemia
DNAM-1
NK cells
NKT-like cells
TACTILE
T cells
url https://www.mdpi.com/2072-6694/12/8/2171
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